Pharmaceutical capsules from improved thermogelling methyl cellulose ethers

• US 4,001,211 A
• Filed: 10/01/1975
• Issued: 01/04/1977
• Est. Priority Date: 12/02/1974
• Status: Expired due to Term

• Current Assignee: The Dow Chemical Company (Dow, Inc.)
• Original Assignee: The Dow Chemical Company (Dow, Inc.)
• Inventors: Sarkar, Nitis
• Primary Examiner(s): Griffin, Ronald W.
• Application Number:
  US05/618,549
• Time in Patent Office: 461 Days
• Field of Search: 260/231 A, 260/231 R, 264/25, 264/301, 264/DIG. 37, 424/35, 106/170, 106/197 R
• US Class Current: 536/84
• CPC Class Codes: A61K 9/4816 Wall or shell material
• CPC Class Codes: Y10S 264/37 Processes and molds for making capsules

Abstract

Improved thermogelling methyl cellulose ether compositions for use in preparing pharmaceutical capsules by the pin dip coating process are prepared by blending the properties of water soluble methyl and C₂ -C₃ hydroxyalkyl cellulose ethers to achieve an essentially Newtonian dip coating solution and a rapid high thermal gel yield strength. These properties require a cellulose ether with a relatively narrow molecular weight distribution. Blends of low viscosity methyl cellulose and hydroxypropylmethyl cellulose provide particularly suitable dip solution properties, gel yield strength, and capsule dissolution rates.

Claims

1. A thermal gelling methyl cellulose ether composition suitable for use in preparing pharmaceutical capsules by an aqueous dip coating process using preheated pins and having a methoxyl DS of about 1.5-2.0, a C₂ -C₃ hydroxyalkyl MS of about 0.1-0.4, a 2 wt. % aqueous solution viscosity of about 2-10 cps at 20°

C and a thermal gel point of about 50°

-80°

C, and a 15-30 wt. % aqueous solution viscosity of about 1,000-10,000 cps at 20°

C, said composition being further characterized by having as a 15- 30 wt. % aqueous solution;

A. essentially Newtonian fluid properties as defined by a power law coefficient, n, of 0.9-1.0 at shear rates of between 0.1-10 sec^-1, and

B. a 50 sec gel yield strength of at least 150 dynes/cm² at 65°

C.

2. The cellulose ether composition of claim 1 where the cellulose ether is a blend of a methyl cellulose having a methoxyl DS of about 1.64-1.90 and a non-ionic C₂ -C₃ hydroxyalkyl cellulose ether.

3. The cellulose ether composition of claim 2 where the non-ionic hydroxyalkyl cellulose ether has a thermal gel point of about 50°

-90°

C as a 2 percent aqueous solution.

4. The cellulose ether composition of claim 2 where the non-ionic cellulose ether is a hydroxypropylmethyl cellulose ether with a 2 percent aqueous solution viscosity of about 2-10 cps at 20°

C.

5. The cellulose ether composition of claim 2 where the cellulose ether is a blend of (1) about 20-50 weight percent of methyl cellulose having a methoxyl DS of about 1.64-1.90 and (2) about 80-50 weight percent of a hydroxypropylmethyl cellulose having a methoxyl DS of about 1.68-1.80 and a hydroxypropoxyl MS of about 0.17-0.30.

6. The cellulose ether composition of claim 1 where the cellulose ether is a hydroxypropylmethyl cellulose ether with a methoxyl DS of about 1.50-2.00, a hydroxypropoxyl MS of about 0.1-0.3, and a 2 percent aqueous solution viscosity of about 2-10 cps at 20°

C.

7. The cellulose ether composition of claim 1 where the cellulose ether has a narrow molecular weight distribution with a M_w /M_n ratio less than about 3.5 and contains less than 0.1 wt % of material having a molecular weight above about 200,000.

8. In a process for preparing pharmaceutical capsules by an aqueous dip coating process using preheated pins and an aqueous bath containing about 15-30 wt. % of a thermal gelling methyl cellulose ether composition having a methoxyl DS of about 1.5-2.0, a C₂ -C₃ hydroxyalkoxyl MS of about 0.1-0.4, a 2 wt. % aqueous solution viscosity of about 2-10 cps at 20°

C and thermal gel point of about 50°

-80°

C, and a 15-30 wt. % aqueous solution viscosity of about 1,000-10,000 cps at 20°

C, the improvement comprising using a methyl cellulose ether composition further characterized by having as a 15-30 wt. % aqueous solution;

A. essentially Newtonian fluid properties as defined by a power law coefficient, n, of 0.9-1.0 at shear rates of between 0.1-10 sec^-1, and

B. a 50 sec gel yield strength of at least 150 dynes/cm² at 65°

C,

as the shell forming component of the aqueous dip coating bath.

9. The process of claim 8 where the cellulose ether has a 50 sec gel yield strength of 150-300 dynes/cm² at 65°

C.

10. The process of claim 8 where size No. 1 capsule pins preheated to about 50°

-60°

C are dipped into a 20-30 wt % aqueous solution of a blend of (1) about 73 wt % of a hydroxypropylmethyl cellulose having a methoxyl DS of about 1.68-1.80 and a hydroxypropoxyl MS of about 0.17-0.30 and (2) about 27 wt % of methyl cellulose having a methoxyl DS of about 1.64-1.90 and the resulting dip coated pins are oven dried at about 45°

-80°

C to give capsule shells having a wall thickness of about 4±

0.5 mils.